Biosensor electrodes prepared by physical vapor deposition

ABSTRACT

A biosensor component is provided that provides enhanced characteristics for use in biosensors, such as blood glucose sensors. The biosensor component comprises a substrate, a conductive layer deposited on the substrate, and a resistive material layer deposited on the conductive layer. The conductive layer includes nickel, chromium, and iron, such that a combined weight percent of the nickel and chromium in the conductive layer is in the range of 25 to less than 95 weight percent, the weight percent of nickel in the conductive layer is at least 4 weight percent, the weight percent of chromium in the conductive layer is at least 10 weight percent, the weight percent of iron in the conductive layer at least 2 weight percent, and such that the conductive layer comprises 0 to 20 weight percent molybdenum.

This application is the national stage filing under 35 U.S.C. § 371 of PCT/US2017/049312, filed Aug. 30, 2017, which claims priority to U.S. Provisional Application No. 62/395,412, filed Sep. 16, 2016, the contents of which are incorporated herein by reference in their entirety.

BACKGROUND Field of the Invention

The present invention is generally related to electrodes, for example, physical vapor deposited components for electrodes such as those found in biosensors. More particularly, the present invention is related to electrodes formed with non-noble metal alloys, for example, those found in biosensor components.

DESCRIPTION OF THE RELATED ART

Biosensors for use in analyzing biological samples are becoming increasingly prevalent. For example, with the rise in cases of diabetes in the world's population, the need for biosensors for measuring blood glucose has risen dramatically. Such biosensors are generally known as glucometers and operate by having a user place a drop of blood on a test-strip associated with the glucometer. The test-strip is configured to be reactive to the amount of glucose in the drop of blood, such that the glucometer can detect and display a glucose level of the user's blood.

The test-strips for glucometer-type biosensors are generally formed with two or more electrodes (e.g., a working electrode and a counter electrode) formed on a substrate. In addition, a bio-reactant that reacts with the biological sample, e.g., an enzyme (e.g., glucose oxidase, glucose dehydrogenase, or the like), and a mediator (e.g., ferricyanide, ruthenium complexes, osmium complexes, quinones, phenothiazines, phenoxazines, or the like) will be formed on one or both electrodes, e.g., the working electrode. In operation of a glucometer-type biosensor, a drop of blood will be applied to a test-strip. Thereafter, an electrochemical reaction proportional to the amount of glucose in the blood will take place on the working electrode. In more detail, glucose first reacts with the bio-reactant, e.g., enzyme (glucose oxidase, glucose dehyrogenase, or the like) and sometimes an enzyme cofactor (PQQ, FAD, or the like) and is oxidized to gluconic acid. The bio-reactant, e.g., enzyme, cofactor, or enzyme-cofactor complex, is temporarily reduced by two electrons transferred from glucose to the enzyme, cofactor, or enzyme-cofactor complex. Next, the reduced bio-reactant, e.g., enzyme, cofactor, or enzyme-cofactor complex, reacts with the mediator, transferring a single electron to each of two mediator species (molecules or complexes), in the case of a mediator that is reduced in a one-electron process. When the mediator species are reduced, the enzyme, cofactor, or enzyme-cofactor complex is thus returned to its original oxidation state. Then, the reduced mediators diffuse to the electrode surface where a pre-determined and sufficiently oxidizing potential is applied to the biosensor so that the reduced mediators are oxidized back to their original oxidation state. The current that is generated by the oxidation of the mediator species by the biosensor is measured and related proportionally to the amount of glucose in the blood.

The quality of the working electrode plays an important role in an accurate measurement of the glucose level of the blood. Specifically, the reproducibility of the electroactive surface area of the electrode, the lot-to-lot repeatability of the electron transfer kinetics of the electrode in a particular glucose measurement arrangement, and long term stability of the electrode material while in storage so that the electrochemical signal that arises from the electrode when the assay is in operation are all factors that lead to improved accuracy of blood glucose test strips. Particularly, it is important that the electrical signals resulting from the electro-activity of the electrode is minimized to prevent bias or noise in the measurement and analysis of biological samples. Typically, this is accomplished by using electrode materials that are intrinsically thermodynamically noble, such as gold, palladium, platinum, iridium, and the like. As such, most current glucometers use electrodes formed from substrates coated with palladium, gold, or other noble metals, generally in the purest form commercially feasible, to function as the working electrode, and for ease of manufacturing, often for the counter electrode or a combined counter and reference electrode. Such noble metals are minimally reactive with interfering substances, and as a result, offer enhanced chemical resistance for consistent and accurate measurements. However, the cost of using such noble metals in electrodes can be prohibitive.

There have been some attempts to use electrodes formed with non-noble metals, so as to reduce manufacturing costs of biosensors. However, such non-noble metal electrodes will generally have an electrochemical response (e.g., dose-responses) that deviates significantly from the electrochemical response of electrodes formed with noble metals. Non-precious materials typically are not anodically stable enough to be used for electrochemical test strips because of high background currents generated when operating at typical voltages of biosensors. In addition, non-precious materials typically do not have facile heterogeneous electron transfer with the desired analyte. As such, electrodes formed with non-noble metals are generally inadequate for use as direct replacements for noble metals in test-strips for many types of biosensors. In addition to having a low electrical response, it is also desirable for a biosensor electrode to have sufficient electron transfer kinetics with the mediator. While some suggested non-noble metals have a relatively low electrochemical response (or reasonable anodic stability), they do not also have acceptable electron transfer kinetics with a mediator.

Accordingly, there is a need for an electrode which can provide consistent and accurate measurements, while providing a cost effective alternative to the use of noble metals, for example, in biosensors. In particular, there is a need for an electrode formed from a non-noble metal alloy that can be used in a biosensor component to consistently and accurately measure biological samples.

SUMMARY

It has been found that non-precious metals can undergo aging phenomenon when exposed to atmospheric conditions resulting in variations in their performance for biosensor applications. It has also been found that electrodes formed by depositing non-precious metals on a substrate film require a sufficient degree of mechanical robustness to achieve adequate performance for biosensor applications. Thus, there is a need for an electrode formed from a non-noble metal alloy that can be used in a biosensor component to consistently and accurately measure biological samples, and which has good mechanical robustness to allow processing and achieve or maintain electrical performance.

One or more embodiments of the present disclosure can relate to an electrode which can comprise a substrate, at least one non-precious metal alloy conductive layer deposited on the substrate, and at least one resistive material layer deposited on the non-precious metal layer. The conductive layer can comprise nickel and chromium wherein the nickel is present in an amount of at least 4, or 5, or 6, or 8 weight percent and the chromium is present in an amount of at least 10 weight percent, based on the weight of the conductive layer.

In one embodiment, the conductive layer can comprise nickel and chromium wherein the combined weight percent of the nickel and chromium in the conductive layer can be in the range of 25 to less than 95 weight percent, at least 10 weight percent chromium, and at least 4, or 5, or 6, or 8 weight percent nickel, based on the total weight of the conductive layer. In addition to nickel and chromium, the conductive layer can also comprise iron wherein the iron is present in an amount greater than 2 weight percent, based on the total weight of the conductive layer equaling 100 weight percent. In embodiments, the conductive layer can comprise 0 to less than 20, or 0 to 17, or 0 to 13, or 0 to 10, or 0 to 9, or 0 to 8, or 0 to 7, or 0 to 6, or 0 to 5, or 0 to 4, or 0 to 3, or 0 to 2, or 0 to 1, or 0 to 0.5, or 0 to 0.1, weight percent molybdenum. While most of this disclosure relates to electrodes used as biosensor components, it is contemplated that the electrodes can be used in other end-use applications as well. As a result, any disclosure herein related to electrodes used in biosensors is intended to incorporate herein applicability to all electrodes that this technology could reasonably be applied to by one of ordinary skill in the art.

In a first aspect, the conductive layer can comprise nickel and chromium wherein the combined weight percent of the nickel and chromium in the conductive layer can be in the range of 25 to 90 weight percent, or 26 to 89 weight percent, based on the total weight of the conductive layer equaling 100 weight percent. In addition to nickel and chromium, the conductive layer can also comprise iron wherein the weight percent of the iron in the conductive layer can be in the range of greater than 5 weight percent to less than 75 weight percent, or about 6 to about 74 weight percent, based on the total weight of the conductive layer equaling 100 weight percent.

In embodiments of the first aspect, the conductive layer can comprise nickel in the range of greater than 7 weight percent and chromium in the range of greater than 13 to less than 21 weight percent and wherein the total combined weight percent of the nickel and chromium in the conductive layer is in the range of greater than 25 to less than 90 weight percent, or 26 to 89 weight percent, based on the total weight of the conductive layer equaling 100 weight percent.

In further embodiments of the first aspect, the conductive layer can comprise nickel in the range of 8 to 72 weight percent, chromium in the range of about 14 to about 20 weight percent, and iron in the range of about 6 to about 74 weight percent and wherein the total combined weight percent of the nickel and chromium in the conductive layer is in the range of about 25 to about 90 weight percent, or 26 to 89 weight percent, based on the total weight of the conductive layer equaling 100 weight percent.

In certain embodiments of the first aspect, the conductive layer can comprise nickel in the range of 8 to 72 weight percent, chromium in the range of 14 to 20 weight percent, and iron in the range of 6 to 74 weight percent, based on the total weight of the conductive layer equaling 100 weight percent.

In certain embodiments of the first aspect, the conductive layer can comprise nickel in the range of 8 to 72 weight percent, chromium in the range of 14 to 20 weight percent, and iron in the range of 6 to 74 weight percent, based on the total weight of the conductive layer equaling 100 weight percent, and wherein the conductive layer does not include any other element species that is present in an amount greater than 2 weight percent, based on the total weight of the conductive layer equaling 100 weight percent. In one embodiment, the conductive layer further comprises manganese in the range of 0.01 to 2.0 weight percent, and does not include any other element species that is present in an amount greater than 1.0 weight percent, based on the total weight of the conductive layer equaling 100 weight percent.

In certain embodiments of the first aspect, the conductive layer can comprise nickel in the range of 8 to 72 weight percent, chromium in the range of 14 to 20 weight percent, and iron in the range of 6 to 74 weight percent, based on the total weight of the conductive layer equaling 100 weight percent, and wherein the conductive layer further comprises manganese in the range of 0.01 to 2.0 weight percent, silicon in the range of 0.01 to 1.0 weight percent, copper in the range of 0 to 0.5 weight percent, based on the total weight of the conductive layer equaling 100 weight percent. In an embodiment, the conductive layer contains less than 0.2 weight percent of each of the following element species: carbon, sulfur, phosphorous, molybdenum, niobium, cobalt, aluminum, titanium, or boron. In an embodiment, the conductive layer contains none, or is substantially free, of the following element species: molybdenum, niobium, cobalt, aluminum, titanium, or boron. In an embodiment, the conductive layer contains none of the following element species: molybdenum, niobium, cobalt, aluminum, titanium, or boron.

In a second aspect, the conductive layer can comprise nickel and chromium wherein the combined weight percent of the nickel and chromium in the conductive layer can be in the range of 80 to less than 95 weight percent, or 81 to 94 weight percent, or 82 to 94 weight percent, or 83 to 94 weight percent, or 85 to 94 weight percent, or 86 to 94 weight percent, based on the total weight of the conductive layer equaling 100 weight percent. In addition to nickel and chromium, the conductive layer can also comprise iron wherein the weight percent of the iron in the conductive layer can be in the range of greater than 5 weight percent to less than 12 weight percent, or about 6 to about 11 weight percent, or 6 to 11 weight percent, or 6 to 10 weight percent, or 6 to 9 weight percent, or 7 to 10 weight percent, or 7 to 9 weight percent, or about 9 weight percent, based on the total weight of the conductive layer equaling 100 weight percent.

In embodiments of the second aspect, the conductive layer can comprise nickel in the range of greater than 70 weight percent and chromium in the range of greater than 13 to less than 20 weight percent and wherein the total combined weight percent of the nickel and chromium in the conductive layer is in the range of greater than 80 to less than 95 weight percent, or 81 to 94 weight percent, or 82 to 94 weight percent, or 83 to 94 weight percent, or 85 to 94 weight percent, or 86 to 94 weight percent, based on the total weight of the conductive layer equaling 100 weight percent.

In further embodiments of the second aspect, the conductive layer can comprise nickel in the range of 70 to 81 weight percent, chromium in the range of about 14 to about 19 weight percent, and iron in the range of about 6 to about 11 weight percent and wherein the total combined weight percent of the nickel and chromium in the conductive layer is in the range of about 84 to about 94 weight percent, or 85 to 94 weight percent, or 86 to 94 weight percent, based on the total weight of the conductive layer equaling 100 weight percent.

In certain embodiments of the second aspect, the conductive layer can comprise nickel in the range of 70 to 81 weight percent, chromium in the range of 14 to 17 weight percent, and iron in the range of 6 to 11 weight percent, based on the total weight of the conductive layer equaling 100 weight percent.

In certain embodiments of the second aspect, the conductive layer can comprise nickel in the range of 72 to 81 weight percent, chromium in the range of 14 to 17 weight percent, and iron in the range of 6 to 11, or 6 to 10, weight percent, based on the total weight of the conductive layer equaling 100 weight percent, and wherein the conductive layer does not include any other element species that is present in an amount greater than 1 weight percent, based on the total weight of the conductive layer equaling 100 weight percent. In one embodiment, the conductive layer further comprises manganese in the range of 0.01 to 1.0 weight percent, and does not include any other element species that is present in an amount greater than 0.5 weight percent, based on the total weight of the conductive layer equaling 100 weight percent.

In certain embodiments of the second aspect, the conductive layer can comprise nickel in the range of 72 to 81 weight percent, chromium in the range of 14 to 17 weight percent, and iron in the range of 6 to 11, or 6 to 10, weight percent, based on the total weight of the conductive layer equaling 100 weight percent, and wherein the conductive layer further comprises manganese in the range of 0.01 to 1.0 weight percent, copper in the range of 0.01 to 0.5 weight percent, and silicon in the range of 0.01 to 0.5 weight percent, based on the total weight of the conductive layer equaling 100 weight percent. In an embodiment, the conductive layer contains none or is substantially free of the following element species: molybdenum, niobium, cobalt, aluminum, titanium, phosphorus, or boron, or, if any species is present, such species is in an amount of less than 0.25 weight percent, or less than 0.2 weight percent, or less than 0.1 weight percent, or less than 0.05 weight percent, or trace amounts or less. In an embodiment, the conductive layer contains none, or is substantially free, of the following element species: molybdenum, niobium, cobalt, aluminum, titanium, phosphorus, or boron.

In a third aspect, the conductive layer can comprise nickel and chromium wherein the combined weight percent of the nickel and chromium in the conductive layer can be in the range of 25 to less than 32 weight percent, or 26 to 31 weight percent, or 26 to 30.5 weight percent, based on the total weight of the conductive layer equaling 100 weight percent. In addition to nickel and chromium, the conductive layer can also comprise iron wherein the weight percent of the iron in the conductive layer can be in the range of at least 65 weight percent to less than 75 weight percent, or greater than 65 weight percent to less than 75 weight percent, or about 66 to about 74 weight percent, or greater than 66 up to 74 weight percent, based on the total weight of the conductive layer equaling 100 weight percent.

In embodiments of the third aspect, the conductive layer can comprise nickel in the range of 7 to less than 12 weight percent and chromium in the range of greater than 16 to less than 22 weight percent and wherein the total combined weight percent of the nickel and chromium in the conductive layer is in the range of 25 to less than 32 weight percent, or 26 to 31 weight percent, or 26 to 30.5 weight percent, based on the total weight of the conductive layer equaling 100 weight percent.

In further embodiments of the third aspect, the conductive layer can comprise nickel in the range of 8 to 11 weight percent, chromium in the range of about 18 to about 20 weight percent, and iron in the range of about 66 to about 74 weight percent and wherein the total combined weight percent of the nickel and chromium in the conductive layer is in the range of about 26 to about 31 weight percent, or 26 to 30.5 weight percent, based on the total weight of the conductive layer equaling 100 weight percent.

In certain embodiments of the third aspect, the conductive layer can comprise nickel in the range of 8 to 10.5 weight percent, chromium in the range of 18 to 20 weight percent, and iron in the range of 66 to 74 weight percent, based on the total weight of the conductive layer equaling 100 weight percent.

In certain embodiments of the third aspect, the conductive layer can comprise nickel in the range of 8 to 10.5 weight percent, chromium in the range of 18 to 20 weight percent, and iron in the range of 66 to 74, weight percent, based on the total weight of the conductive layer equaling 100 weight percent, and wherein the conductive layer does not include any other element species that is present in an amount greater than 1 weight percent, based on the total weight of the conductive layer equaling 100 weight percent. In one embodiment, the conductive layer further comprises manganese in the range of 0.01 to 1.0 weight percent and silicon in the range of 0.01 to 1.0 weight percent, and does not include any other element species that is present in an amount greater than 0.2, or 0.1, weight percent, based on the total weight of the conductive layer equaling 100 weight percent.

In certain embodiments of the third aspect, the conductive layer can comprise nickel in the range of 8 to 10.5 weight percent, chromium in the range of 18 to 20 weight percent, and iron in the range of 66 to 74, weight percent, based on the total weight of the conductive layer equaling 100 weight percent, and wherein the conductive layer further comprises manganese in the range of 0.01 to 1.0 weight percent, silicon in the range of 0.01 to 1.0 weight percent, and further comprises carbon, sulfur and phosphorous each in an amount less than 0.1 weight percent, based on the total weight of the conductive layer equaling 100 weight percent. In an embodiment, the conductive layer contains none or is substantially free of the following element species: molybdenum, niobium, cobalt, aluminum, titanium, copper or boron, or, if any species is present, such species is in an amount of less than 0.25 weight percent, or less than 0.2 weight percent, or less than 0.1 weight percent, or less than 0.05 weight percent, or trace amounts or less. In an embodiment, the conductive layer contains none, or is substantially free, of the following element species: molybdenum, niobium, cobalt, aluminum, titanium, copper or boron.

In certain embodiments of the present disclosure, the conductive layer can be coated on the substrate, that can be comprised of at least one of any polymer described in the art and/or described herein including but not limited to polycarbonate, silicone polymers, acrylics, PET, modified PET such as PETG or PCTG, PCT, modified PCT, polyesters comprising TMCD AND CHDM, PCCD, or PEN, by physical vapor deposition.

In certain embodiment of the disclosure, the resistive material layer can comprise a thin film of resistive material deposited on the surface of the conductive layer. By the term “resistive material” is meant a material that is more electrically resistive than the conductive layer, allows current to flow upon application of a constant potential, and, when formed into a thin film electrode having a conductive layer and a resistive material layer on the conductive layer, increases the electrode's anodic stability and/or increases electron transfer kinetics, as determined by a Type 1 Linear Sweep Voltammetry Test, compared to a similar electrode with just the conductive layer.

In certain embodiments, the resistive material layer can comprise one or more elements chosen from carbon, silicon, boron, oxygen, and combinations thereof. In certain embodiments, the resistive material layer comprises carbon. In certain embodiments, the resistive material layer comprises amorphous carbon. In certain embodiments, the resistive material layer is amorphous carbon deposited by sputtering. In certain embodiments, the resistive material layer is amorphous carbon deposited by sputtering using a carbon source. In certain embodiments, the resistive material layer is amorphous carbon deposited by sputtering using a carbon source in a separate sputtering step than a sputtering step used to deposit the conductive layer (i.e., there is no co-sputtering of the conductive layer and carbon layer being performed).

In certain embodiments, the resistive layer comprises amorphous carbon that is composed primarily of sp² hybridized carbon, sp³ hybridized carbon, or combinations thereof. In certain embodiments, an amorphous carbon layer composed primarily of sp² hybridized carbon, sp³ hybridized carbon, or combinations thereof can be formed using techniques/processes as suggested by: Onoprienko, A. A., Shaginyan, L. R., Role of microstructure in forming thin carbon film properties. Diamond Relat. Mater. 1994, 3, 1132-1136; Onoprienko, A., In Carbon, The Future Material for Advanced Technology Applications; Messina, G., Santangelo, S., Eds.; Springer Berlin Heidelberg, 2006; or Cho, N. H.; Krishnan, K. M.; Veirs, D. K.; Rubin, M. D.; Hopper, C. B.; Bhushan, B.; Bogy, D. B. Chemical structure and physical properties of diamond-like amorphous carbon films prepared by magnetron sputtering. J. Mater. Res. 1990, 5, 2543-2554.

In certain embodiments of the disclosure, the resistive material layer can have a thickness in the range from 5 to 200 nm, the conductive layer can have a thickness in the range from 15 and 200 nm, and the substrate can have a thickness in the range from 25 and 500 μm. In certain embodiments, the biosensor component can also have visible light transmission of no more than 20% or no more than 15% or no more than 10% or no more than 5 or from 0.01 to 20% or from 0.01 to 15% or from 0.01 10% or from 0.01 to 5%, as measured by ASTM D1003.

In certain embodiments of the disclosure, the resistive material layer can have a thickness in the range from 5 to 200 nm, the conductive layer can have a thickness in the range from 15 and 200 nm, and the substrate can have a thickness in the range from 25 and 500 μm wherein the biosensor component has a visible light transmission of no more than 20%.

In certain embodiments of the disclosure, the resistive material layer can have a thickness in the range from 5 to 200 nm, the conductive layer can have a thickness in the range from 15 and 200 nm, and the substrate can have a thickness in the range from 25 and 500 μm wherein the biosensor component has a visible light transmission of no more than 15%.

In certain embodiments of the disclosure, the resistive material layer can have a thickness in the range from 5 to 200 nm, the conductive layer can have a thickness in the range from 15 and 200 nm, and the substrate can have a thickness in the range from 25 and 500 μm wherein the biosensor component has a visible light transmission of no more than 10%.

In certain embodiments of the disclosure, the resistive material layer can have a thickness in the range from 5 to 200 nm, the conductive layer can have a thickness in the range from 15 and 200 nm, and the substrate can have a thickness in the range from 25 and 500 μm wherein the biosensor component has a visible light transmission of no more than 5%.

In certain embodiments, the resistive material layer has a thickness in the range from 5 to 100 nm, or 5 to 50 nm, or 5 to 30 nm, or 5 to 25 nm, or 5 to 20 nm, or 5 to less than 20 nm, or 5 to 15 nm. In embodiments, the resistive material layer is amorphous carbon and has a thickness in the range from 5 to 100 nm, or 5 to 50 nm, or 5 to 30 nm, or 5 to 25 nm, or 5 to 20 nm, or 5 to less than 20 nm, or 5 to 15 nm. In embodiments, the resistive material layer is amorphous carbon and has a thickness in the range from 5 to 20 nm, or 5 to less than 20 nm, or 5 to 15 nm.

In one aspect, certain embodiments of the present disclosure relate to a biosensor component comprising a substrate, a conductive layer deposited on the substrate, and a resistive material layer deposited on the conductive layer, wherein the resistive material layer can comprise carbon, the conductive layer can comprise nickel and chromium in a combined weight in the range of 25 to less than 95 weight percent, chromium in an amount of at least 10 weight percent, nickel in an amount of at least 8 weight percent, iron in an amount of at least 2 weight percent, and molybdenum in an amount in the range from 0 to 20 weight percent, based on the total weight of the conductive layer equaling 100 weight percent, and the substrate can be comprised of at least one of any polymer described in the art and/or described herein including but not limited to polycarbonate, silicone polymers, acrylics, PET, modified PET such as PETG or PCTG, PCT, PCTA, polyesters comprising TMCD AND CHDM, PCCD, or PEN, by any means known in the art, including but not limited to, physical vapor deposition. In embodiments, the resistive layer can have a thickness in the range of 5 to 100 nm, the conductive layer can have a thickness of between 15 and 200 nm, and the substrate can have a thickness of between 25 and 500 μm, such that the biosensor component has a visible light transmission of no more than 20% or no more than 15% or no more than 10% or no more than 5%.

One or more embodiments of the present disclosure can relate to an electrode for a biosensor, with the electrode comprising a substrate, a conductive layer deposited on the substrate, and a resistive material layer deposited on the conductive layer. In certain embodiments, the conductive layer can comprise nickel and chromium, and the conductive layer can have an oxidation wave voltage for Fe(II)[CN]₆ mediator (identified below as E_(peak,anodic)) of less than 1000, or less than 950, or less than 925, or less than about 900 millivolts (mV), as determined in a Type 1 Linear Sweep Voltammetry Test (as discussed in the Examples section). In certain embodiments, the conductive layer can comprise nickel and chromium, and the conductive layer can have an oxidation wave voltage for Fe(II)[CN]₆ mediator (identified below as E_(peak,anodic)) of less than 450, or less than 400, or less than 375, or less than 350, or less than 325, or less than 300, or less than 275 millivolts (mV), as determined in a Type 1 Linear Sweep Voltammetry Test (as discussed in the Examples section).

In one aspect, embodiments of the present disclosure can relate to an electrode for a biosensor, with the electrode comprising a substrate, a conductive layer deposited on the substrate, and a resistive material (e.g., amorphous carbon) layer deposited on the conductive layer, wherein the conductive layer can comprise nickel, chromium, and iron (as described in the various aspects and embodiments above), and wherein the electrode can have an oxidation wave voltage for Fe(II)[CN]₆ mediator (identified below as E_(peak,anodic)) of less than 1000, or less than 950, or less than 925, or less than about 900 millivolts (mV), as determined in a Type 1 Linear Sweep Voltammetry Test (as discussed in the Examples section). In embodiments, the conductive layer can comprise nickel, chromium, and iron (as described in the various aspects and embodiments above), and wherein the electrode can have an oxidation wave voltage for Fe(II)[CN]₆ mediator (identified below as E_(peak,anodic)) of less than 450, or less than 400, or less than 375, or less than 350, or less than 325, or less than 300, or less than 275 millivolts (mV), as determined in a Type 1 Linear Sweep Voltammetry Test (as discussed in the Examples section). In one embodiment, the conductive layer can comprise nickel in amount of at least 8 weight percent, chromium in the amount of at least 10 weight percent, wherein the combined weight percent of the nickel and chromium in the conductive layer can be in the range of 25 to 95 weight percent, and wherein the conductive layer can comprise iron in an amount in a range of at least 2 weight percent and molybdenum in an amount from 0 to 20 weight percent, based on the total weight of the conductive layer equaling 100 weight percent. In another embodiment, the conductive layer can comprise nickel in amount from 8 to 72 weight percent, chromium in the amount from 14 to 20 weight percent, wherein the combined weight percent of the nickel and chromium in the conductive layer can be in the range of 25 to 90 weight percent, and wherein the conductive layer can comprise iron in an amount in a range of at least 2 to 75 weight percent and molybdenum in an amount from 0 to 20, or 0 to 10, or 0 to 5, or 0 to 2, or 0 to 1 weight percent, based on the total weight of the conductive layer equaling 100 weight percent.

In one aspect, embodiments of the present disclosure can relate to an electrode for a biosensor, with the electrode comprising a substrate, a conductive layer deposited on the substrate, and a resistive material layer deposited on the conductive layer, wherein the conductive layer can comprise nickel, chromium, and iron, and can have an oxidation wave voltage for Fe(II)[CN]₆ mediator (identified below as E_(peak,anodic)) of less than 400, or less than 375, or less than 350, or less than 325, or less than 300, or less than 275 millivolts (mV), as determined in a Type 1 Linear Sweep Voltammetry Test (as discussed in the Examples section), and wherein the conductive layer can comprise nickel in amount greater than 70 weight percent, chromium in the range of greater than 13 to less than 18 weight percent, wherein the combined weight percent of the nickel and chromium in the conductive layer can be in the range of 83 to 94 weight percent, or 84 to 94 weight percent, or 85 to 94 weight percent, or 86 to 94 weight percent, and wherein the conductive layer can comprise iron in an amount in a range from greater than 5 to less than 12 weight percent, or from 6 to 11 weight percent, based on the total weight of the conductive layer equaling 100 weight percent.

In one aspect, embodiments of the present disclosure can relate to an electrode for a biosensor, with the electrode comprising a substrate, a conductive layer deposited on the substrate, and a resistive material layer deposited on the conductive layer, wherein the conductive layer can comprise nickel, chromium, and iron, and can have an oxidation wave voltage for Fe(II)[CN]₆ mediator (identified below as E_(peak,anodic)) of less than 400, or less than 375, or less than 350, or less than 325, or less than 300, or less than 275 millivolts (mV), as determined in a Type 1 Linear Sweep Voltammetry Test (as discussed in the Examples section), and wherein the conductive layer can comprise nickel in amount from 7 to less than 12 weight percent, chromium in the range of greater than 16 to less than 22 weight percent, wherein the combined weight percent of the nickel and chromium in the conductive layer can be in the range of 25 to 32 weight percent, or 26 to 31 weight percent, or 26 to 30.5 weight percent, and wherein the conductive layer can comprise iron in an amount in a range from 65 to less than 75 weight percent, or from 66 to 74 weight percent, based on the total weight of the conductive layer equaling 100 weight percent.

The substrate can be comprised of any polymer composition known in the art including but not limited to at least one polymer selected from the groups consisting of: nylon, polyesters, copolyesters, polyethylene, polypropylene, polyamides; polystyrene, polystyrene copolymers, styrene acrylonitrile copolymers, acrylonitrile butadiene styrene copolymers, poly(methylmethacrylate), acrylic copolymers, poly(ether-imides); polyphenylene oxides or poly(phenylene oxide)/polystyrene blends, polystyrene resins; polyphenylene sulfides; polyphenylene sulfide/sulfones; poly(ester-carbonates); polycarbonates; polysulfones; polysulfone ethers; and poly(ether-ketones); or mixtures of any of the other foregoing polymers.

In one embodiment, the substrate can be comprised of at least one polyester comprising residues of at least one glycol selected from the group consisting of ethylene glycol, 1,4-cyclohexanedimethanol, and 2,2,4,4-tetramethyl-1,3-cyclobutanediol.

In one embodiment, the substrate can be comprised of at least one polyester comprising residues of terephthalic acid and/or dimethyl terephthalate and residues of at least one glycol selected from the group consisting of ethylene glycol, 1,4-cyclohexanedimethanol, and 2,2,4,4-tetramethyl-1,3-cyclobutanediol.

In one embodiment, the substrate can be comprised of at least one polyester comprising an acid component which comprises residues of terephthalic acid and isophthalic acid and/or esters thereof such as dimethyl terephthalate, and at glycol component comprising residues of at least one glycol selected from the group consisting of ethylene glycol residues, 1,4-cyclohexanedimethanol residues, and 2,2,4,4-tetramethyl-1,3-cyclobutanediol.

In one embodiment, the substrate can be comprised of at least one polyester comprising terephthalic acid residues, or an ester thereof, or mixtures thereof, and 1,4-cyclohexanedimethanol residues.

In one embodiment, the substrate can be comprised of at least one polyester made from terephthalic acid residues, or an ester thereof, or mixtures thereof, and 1,4-cyclohexanedimethanol residues and/or 2,2,4,4-tetramethyl-1,3-cyclobutanediol residues.

In one embodiment, the substrate can be comprised of at least one polyester made from terephthalic acid residues, or an ester thereof, or mixtures thereof, 2,2,4,4-tetramethyl-1,3-cyclobutanediol residues, and 1,4-cyclohexanedimethanol residues.

In one embodiment, the substrate can be comprised of at least one polyester made from terephthalic acid residues, or an ester thereof, or mixtures thereof, 2,2,4,4-tetramethyl-1,3-cyclobutanediol residues, and ethylene glycol residues.

In one embodiment, the substrate can be comprised of at least one polyester comprising terephthalic acid residues, or an ester thereof, or mixtures thereof, ethylene glycol residues, and 1,4-cyclohexanedimethanol residues.

Conductive layers in the present disclosure can be constructed of a single layer comprising any of the alloy compositions disclosed in this application. In certain embodiments, the alloy composition contains an alloy which can be a solid solution of the elements (a single phase), a mixture of metallic phases (two or more solutions) or an intermetallic compound with no distinct boundary between the phases.

One or more embodiments of the present disclosure concern a method for forming an electrode for a biosensor. The method comprises (a) providing a substrate; (b) providing a conductive layer target; (c) physical vapor depositing at least a portion of said substrate with material from said conductive layer target to thereby form a conductive layer on said substrate having a conductive layer surface facing opposite the substrate; (d) providing a target that when used as the source material for physical vapor deposition, produces a resistive material hereafter referred to as “resistive material target”; and (e) physical vapor depositing at least a portion of said conductive layer with material from said resistive material target to thereby form a resistive material layer on said conductive layer surface. For clarity, it should be understood that the resistive material target can have a different composition and/or structure than the deposited resistive material. The conductive material can comprise nickel in the range of at least 8 weight percent, chromium in the range of greater than 10 weight percent and iron in the range of at least 2 weight percent, wherein the total combined weight percent of the nickel and chromium in the conductive layer is in the range of 25 to less than 95 weight percent, or 25 to 90 weight percent, or 26 to 89 weight percent, based on the total weight of the conductive layer equaling 100 weight percent. In one embodiment, the conductive material can comprise molybdenum in the range from 0 to 20 weight percent, based on the total weight of the conductive layer equaling 100 weight percent. The resistive material layer can comprise amorphous carbon and have a thickness in the range from 5 to 100 nm, or 5 to 50 nm, or 5 to 25 nm, or 5 to less than 20 nm. Additionally, the combined conductive layer and resistive material layer can have a sheet resistance of less than 2000 ohms per square.

In one aspect, embodiments of the present disclosure can relate to a method for forming an electrode for a biosensor. The method comprises (a) providing a substrate; (b) providing a conductive layer target; (c) physical vapor depositing at least a portion of said substrate with material from said conductive layer target to thereby form a conductive layer on said substrate having a conductive layer surface facing opposite the substrate; (d) providing a resistive material target; and (e) physical vapor depositing at least a portion of said conductive layer with material from said resistive material target to thereby form a resistive material layer on said conductive layer surface. The conductive material can comprise nickel in the range of 8 to 72 weight percent, chromium in the range of 14 to 20 weight percent and iron in the range of greater than 5 to 75 weight percent, wherein the total combined weight percent of the nickel and chromium in the conductive layer is in the range of 25 to less than 95 weight percent, or 25 to 90 weight percent, or 26 to 89 weight percent, based on the total weight of the conductive layer equaling 100 weight percent. The resistive material layer can comprise amorphous carbon and have a thickness in the range from 5 to 100 nm, or 5 to 50 nm, or 5 to 25 nm, or 5 to less than 20 nm. Additionally, the combined conductive layer and resistive material layer can have a sheet resistance of less than 2000 ohms per square. In addition to nickel, chromium and iron, the conductive layer can also comprise up to 2 weight percent manganese and up to 1 weight percent silicon, based on the total weight of the conductive layer equaling 100 weight percent.

In one aspect, embodiments of the present disclosure relate to a method for forming an electrode for a biosensor. The method comprises (a) providing a substrate; (b) providing a conductive layer target; (c) physical vapor depositing at least a portion of said substrate with material from said conductive layer target to thereby form a conductive layer on said substrate having a conductive layer surface facing opposite the substrate; (d) providing a resistive material target; and (e) physical vapor depositing at least a portion of said conductive layer with material from said resistive material target to thereby form a resistive material layer on said conductive layer surface. The conductive material can comprise nickel and chromium wherein the combined weight percent of the nickel and chromium in the conductive layer can be in the range of 80 to less than 95 weight percent, or 81 to 94 weight percent, or 82 to 94 weight percent, or 83 to 94 weight percent, or 85 to 94 weight percent, or 86 to 94 weight percent, based on the total weight of the conductive layer equaling 100 weight percent. In addition to nickel and chromium, the conductive layer can also comprise iron wherein the weight percent of the iron in the conductive layer can be in the range of greater than 5 weight percent to less than 12 weight percent, or about 6 to about 11 weight percent, or 6 to 11 weight percent, or 6 to 10 weight percent, or 6 to 9 weight percent, or 7 to 10 weight percent, or 7 to 9 weight percent, or about 9 weight percent, based on the total weight of the conductive layer equaling 100 weight percent. The resistive material layer can comprise amorphous carbon and have a thickness in the range from 5 to 100 nm, or 5 to 50 nm, or 5 to 25 nm, or 5 to less than 20 nm. Additionally, the combined conductive layer and resistive material layer can have a sheet resistance of less than 2000 ohms per square.

In one aspect, embodiments of the present disclosure relate to a method for forming an electrode for a biosensor. The method comprises (a) providing a substrate; (b) providing a conductive layer target; (c) physical vapor depositing at least a portion of said substrate with material from said conductive layer target to thereby form a conductive layer on said substrate having a conductive layer surface facing opposite the substrate; (d) providing a resistive material target; and (e) physical vapor depositing at least a portion of said conductive layer with material from said resistive material target to thereby form a resistive material layer on said conductive layer surface. The conductive material can comprise nickel and chromium wherein the combined weight percent of the nickel and chromium in the conductive layer can be in the range of 25 to less than 32 weight percent, or 26 to 31 weight percent, or 26 to 30.5 weight percent, based on the total weight of the conductive layer equaling 100 weight percent. In addition to nickel and chromium, the conductive layer can also comprise iron wherein the weight percent of the iron in the conductive layer can be in the range of 65 weight percent to less than 75 weight percent, or about 66 to about 74 weight percent, or greater than 66 up to 74 weight percent, based on the total weight of the conductive layer equaling 100 weight percent. The resistive material layer can comprise amorphous carbon and have a thickness in the range from 5 to 100 nm, or 5 to 50 nm, or 5 to 25 nm, or 5 to less than 20 nm. Additionally, the combined conductive layer and resistive material layer can have a sheet resistance of less than 2000 ohms per square.

One or more embodiments of the present disclosure concern a method for forming an electrode for a biosensor. The combined conductive layer and resistive material layer can have a sheet resistance, as measured by ASTM F1711-96, of no more than 5000, 2000, 100, 80, 60, 50, 40, 20, 10, or 5 ohms per square. In some embodiments, the layers can have a sheet resistance of between 1 to 5000 ohms per square, 1 to 4000 ohms per square, 1 to 3000 ohms per square, 1 to 2000 ohms per square, 1 to 1000 ohms per square, 1 to 500 ohms per square, 5 to 100 ohms per square, 5 to 20 ohms per square, 5 to 15 ohms per square, 5 to 10 ohms per square, 10 to 80 ohms per square, 20 to 60 ohms per square, or 40 to 50 ohms per square, as measured by ASTM F1711-96. The layers can have a sheet resistance of less than 2000 ohms per square.

BRIEF DESCRIPTION OF THE FIGURES

Embodiments of the present disclosure are described herein with reference to the following figures, wherein:

FIG. 1 is a sectional schematic illustration of a thin-film electrode biosensor component of embodiments of the present disclosure;

FIG. 2 is a schematic illustration of a test-strip biosensor component of embodiments of the present disclosure;

FIG. 3 is a graph depicting a linear sweep voltammogram plot of a thin-film electrode in a mediator-containing solution;

FIG. 4 is a graph depicting a linear sweep voltammogram plot of thin-film electrodes comparing stainless steel 316 with and without a carbon layer in both mediator-free and Fe(II)[CN]₆ mediator-containing buffer solutions;

FIG. 5 is a graph depicting a linear sweep voltammogram plot of thin-film electrodes for various metal alloy conductive layers capped by carbon in Fe(II)[CN]₆ mediator-containing buffer solutions;

FIG. 6 is a graph depicting the effect of bending thin-film electrode over various diameter mandrels (substrate side touching) on sheet resistance for various conductive layer alloys capped with carbon; and

FIG. 7 is a graph depicting the effect of bending thin-film electrode over various diameter mandrels (coated side touching) on sheet resistance for various conductive layer alloys capped with carbon.

DETAILED DESCRIPTION

The present invention is generally directed to a component for an electrode such as those used in a biosensor. As used herein, the term “biosensor” shall denote a device for analyzing biological samples. In some embodiments, as illustrated in FIG. 1 , the biosensor component may be a layered thin-film electrode 100 and may broadly comprise a substrate 102, a conductive layer 104 deposited on at least a portion of the substrate 102, and a resistive material layer 106 deposited on at least a portion of the conductive layer 104. In some embodiments, the biosensor may be a medical sensor, such as a glucose measuring system, and the biosensor component may be a test-strip for use with the biosensor. As used herein, the term “medical sensor” shall denote a biosensor used for medical monitoring and/or diagnosis. For instance, as illustrated in FIG. 2 , some embodiments contemplate that the biosensor component will comprise a test-strip 110 that includes a first electrode 100 separated from a second electrode 100 a by a reaction space 112. The first electrode 100 may comprise a working electrode and the second electrode 100 a may comprise a reference electrode or a counter electrode or a combined reference and counter electrode. As such, a biological sample, such as a drop of blood, can be placed within the reaction space 112 and in electrical contact with the first and second electrodes 100 and 100 a for analysis. It should be understood that FIG. 2 is not intended to be limiting and shows one possible embodiment for a test strip. Other embodiments for test strips can include different configurations for the electrode(s), such as, for example, a co-planar electrode configuration. As used herein, the term “blood glucose sensor” shall denote a medical sensor used to determine a concentration of glucose in blood. In addition, a bio-reactant that reacts with the biological sample, e.g., a protein, an enzyme (e.g., glucose oxidase, glucose dehydrogenase, or the like), and a mediator (e.g., ferricyanide, ruthenium complexes, osmium complexes, quinones, phenothiazines, phenoxazines, or the like) can be formed on one or both electrodes, e.g., the working electrode.

Unlike conventional physical vapor deposited biosensor components, which normally include and/or use noble metals such as palladium and/or gold, the biosensor components described herein can be formed from non-noble metals alloys, such as those including nickel and chromium. Nevertheless, biosensor components, such as thin-film electrodes, formed from the non-noble metals alloys having a resistive material layer deposited thereon, as described herein, can exhibit superior consistency and accuracy when measuring biological samples. Thus, by using biosensor components comprised of the non-noble metal alloys and a resistive material layer, as described herein, the material and manufacturing costs typically associated with the fabrication and use of biosensor components can be significantly reduced.

Embodiments of the present disclosure provide for the substrate 102 to be formed from any type of material, either flexible or rigid, which is generally non-conductive and chemically inert to the contemplated chemical reactions described herein. In certain embodiments, the substrate 102 of the biosensor component may comprise a flexible, non-conductive film, including polymers, such as a polymeric film, a polyester film, a polycarbonate film, or the like. In certain specific embodiments, the substrate 102 may comprise a polyethylene terephthalate (PET) film. Embodiments of the present disclosure contemplate that the substrate 102 may have a thickness of at least 25 μm, 125 μm, or 250 μm, and/or not more than 800 μm, 500 μm, or 400 μm. In certain embodiments, the substrate 102 may have a thickness of between 25 to 800 μm, 25 to 500 μm, or 25 to 400 μm, between 125 to 800 μm, 125 to 500 μm, or 125 to 400 μm, or between 250 to 800 μm, 250 to 500 μm, or 250 to 400 μm.

The conductive layer 104 coated on the substrate 102 may comprise one or more non-noble metals. Such conductive layer 104 may be coated on the substrate 102 via one or more physical vapor deposition techniques, such as sputter coating (e.g., magnetron sputtering, unbalanced magnetron sputtering, facing targets sputtering, or the like), thermal evaporation, electron beam evaporation, laser ablation, arc vaporization, co-evaporation, ion plating, or the like. The conductive layer 104 may be coated on the substrate 102 to a thickness of at least 1, 10, 15, or 30 nm, and/or not more than 1000, 200, 100, or 50, nm. In certain embodiments, the conductive layer 104 may have a thickness of between 1 to 1000 nm, 1 to 200 nm, 1 to 100 nm, or 1 to 50 nm, between 10 to 1000 nm, 10 to 200 nm, 10 to 100 nm, or 10 to 50 nm, between 15 to 1000 nm, 15 to 200 nm, 15 to 100 nm, or 15 to 50 nm, or between 30 to 1000 nm, 30 to 200 nm, 30 to 100 nm, or 30 to 50 nm.

The resistive material layer 106 may be deposited on the conductive layer 104 via one or more physical vapor deposition techniques, such as sputter coating (e.g., magnetron sputtering, unbalanced magnetron sputtering, facing targets sputtering, or the like), thermal evaporation, electron beam evaporation, arc vaporization, co-evaporation, ion plating, plasma enhanced vapor deposition, atomic layer deposition, or the like. In certain embodiments, the resistive material layer 106 may be coated on the substrate 104 to a thickness of at least 1, 5, 10, or 15 nm, and/or not more than 200, 100, 50, 25, 20, an amount less than 20, or 15 nm. In certain embodiments, the resistive layer 106 may have a thickness of from 1 to 200 nm, 1 to 100 nm, 1 to 50 nm, 1 to 20 nm, 1 to less than 20 nm, or 1 to 15 nm; or from 5 to 200 nm, 5 to 100 nm, 5 to 50 nm, 5 to 25 nm, 5 to 20 nm, 5 to less than 20 nm, or 5 to 15 nm; or from 10 to 200 nm, 10 to 100 nm, 10 to 50 nm, or 10 to 25 nm, 10 to 20 nm, 10 to less than 20 nm, or 10 to 15 nm.

The conductive layer 104 and resistive material layer 106 may be deposited on the substrate 102, such that the resulting thin-film electrode 100 will generally be opaque to visible light. For example, the resulting thin-film electrode 100 may have a visible light transmission, as measured by ASTM D1003, of no more than 50%, no more than 40%, no more than 30%, or no more than 20%. In certain embodiments, the resulting thin-film electrode 100 may have a visible light transmission of between 1 to 50%, between 10 to 40%, between 15 to 30%, or about 20%. Additionally, the resulting thin-film electrode 100 may have a sheet resistance, as measured by ASTM F1711-96, of no more than 5000, 2000, 100, 80, 60, 50, 40, 20, 10, or 5 ohms per square. In some embodiments, the resulting thin-film electrode 100 may have a sheet resistance of between 1 to 5000 ohms per square, 2 to 2000 ohms per square, 5 to 100 ohms per square, 10 to 80 ohms per square, 20 to 60 ohms per square, or 40 to 50 ohms per square.

Non-noble metals described herein, which form a conductive layer 104, may be comprised of alloys of nickel and chromium. For example, non-noble metal alloys comprised of at least 4, or 5, or 6, or 8 weight percent nickel and at least 10 weight percent chromium were used to prepare conductive layers 104 of a biosensor component, wherein the conductive layers were further coated by depositing an amorphous carbon resistive material layer 106 on the conductive layer 104. Table 1 includes alloys containing nickel and chromium that were used to prepare electrodes comprising both a conductive layer and an amorphous carbon resistive material layer. Table 1 also includes an electrode having a nickel conductive layer and an amorphous carbon layer. It should be understood that, unless specifically stated otherwise, weight percentages provided herein for elements contained in the conductive layer are based on the total weight of the conductive layer only, and do not include elements contained in the resistive layer.

In addition to the amounts described in Table 1, in certain embodiments, the amount of nickel and chromium included in the non-noble metal alloys that comprise the conductive layer of the electrode (for example, conductive layer 104 of the biosensor component) can vary depending on the specific requirements of the electrode, for example, the biosensor component. In various embodiments, the non-noble metal alloys can comprise at least about 4, or 5, or 6, or 8 to about 72 weight percent of nickel. Additionally, in various embodiments, the non-noble metal alloys can comprise at least about 10, 13, 14, and/or up to about 30, 25, 20, 19, 18, or 17 weight percent of chromium. More particularly, in embodiments, the non-noble metal alloys can comprise in the range of about 12 to 30, 12 to 25, 13 to 20, 13 to 19, 13 to 18, 13 to 17, 14 to 20, 14 to 19, 14 to 18, or 14 to 17 weight percent of chromium.

In certain embodiments, the amount of nickel and chromium included in the non-noble metal alloys that comprise the conductive layer of electrode, for example, the biosensor component, can vary depending on the specific requirements of the biosensor component as follows: 10 to 30 weight % chromium and 4 to 81 weight % nickel; 10 to 30 weight % chromium and 8 to 81 weight % nickel; or 10 to 25 weight % chromium and 8 to 81 weight % nickel; or 12 to 25 weight % chromium and 8 to 81 weight % nickel; or 13 to 23 weight % chromium and 8 to 81 weight % nickel; or 13 to 21 weight % chromium and 8 to 81 weight % nickel, or 14 to 20 weight % chromium and 8 to 81 weight % nickel; or 12 to 25 weight % chromium and 8 to 75 weight % nickel; or 13 to 23 weight % chromium and 8 to 75 weight % nickel; or 13 to 21 weight % chromium and 8 to 75 weight % nickel; or 14 to 20 weight % chromium and 8 to 75 weight % nickel; or 12 to 25 weight % chromium and 8 to 72 weight % nickel; or 13 to 23 weight % chromium and 8 to 72 weight % nickel; or 13 to 21 weight % chromium and 8 to 72 weight % nickel; or 14 to 20 weight % chromium and 8 to 72 weight % nickel. In certain embodiments, these metal alloys can also comprise at least 2 weight % iron; or 2 to 75 weight % iron, or 3 to 75 weight % iron; or 4 to 75 weight % iron; or 5 to 75 weight % iron.

In certain embodiments, the amount of nickel and chromium included in the non-noble metal alloys that comprise the conductive layer of electrode, for example, the biosensor component, can vary depending on the specific requirements of the biosensor component as follows: 12 to 25 weight % chromium and 70 to 81 weight % nickel; or 13 to 20 weight % chromium and 70 to 81 weight % nickel; or 13 to 19 weight % chromium and 70 to 81 weight % nickel; or 13 to 18 weight % chromium and 70 to 81 weight % nickel; or 13 to 17 weight % chromium and 70 to 81 weight % nickel, or 14 to 20 weight % chromium and 70 to 81 weight % nickel; or 14 to 19 weight % chromium and 70 to 81 weight % nickel; or 14 to 18 weight % chromium and 70 to 81 weight % nickel; or 14 to 17 weight % chromium and 70 to 81 weight % nickel; or 13 to 20 weight % chromium and 71 to 81 weight % nickel; or 13 to 19 weight % chromium and 71 to 81 weight % nickel; or 13 to 18 weight % chromium and 71 to 81 weight % nickel; or 13 to 17 weight % chromium and 71 to 81 weight % nickel; or 14 to 20 weight % chromium and 71 to 81 weight % nickel; or 14 to 19 weight % chromium and 71 to 81 weight % nickel; or 14 to 18 weight % chromium and 71 to 81 weight % nickel; or 14 to 17 weight % chromium and 71 to 81 weight % nickel; or 13 to 20 weight % chromium and 72 to 81 weight % nickel; or 13 to 19 weight % chromium and 72 to 81 weight % nickel; or 13 to 18 weight % chromium and 72 to 81 weight % nickel; or 13 to 17 weight % chromium and 72 to 81 weight % nickel; or 14 to 20 weight % chromium and 72 to 81 weight % nickel; or 14 to 19 weight % chromium and 72 to 81 weight % nickel; or 14 to 18 weight % chromium and 72 to 81 weight % nickel; or 14 to 17 weight % chromium and 72 to 81 weight % nickel; or 13 to 18 weight % chromium and 70 to 80 weight % nickel; or 13 to 17 weight % chromium and 70 to 80 weight % nickel; or 14 to 18 weight % chromium and 70 to 80 weight % nickel; or 14 to 17 weight % chromium and 70 to 80 weight % nickel; or 13 to 18 weight % chromium and 71 to 80 weight % nickel; or 13 to 17 weight % chromium and 71 to 80 weight % nickel; or 14 to 18 weight % chromium and 71 to 80 weight % nickel; or 14 to 17 weight % chromium and 71 to 80 weight % nickel; or 13 to 18 weight % chromium and 72 to 80 weight % nickel; or 13 to 17 weight % chromium and 72 to 80 weight % nickel; or 14 to 18 weight % chromium and 72 to 80 weight % nickel; or 14 to 17 weight % chromium and 72 to 80 weight % nickel; all of these weight percentages being based on the total weight percentages of the conductive layer equaling 100 weight percent. In certain embodiments, these metal alloys can also comprise at least 5 weight % iron; or 5 to 12 weight % iron, or 6 to 12 weight % iron; or 6 to 11 weight % iron.

In certain embodiments, the amount of nickel and chromium included in the non-noble metal alloys that comprise the conductive layer of electrode, for example, the biosensor component, can vary depending on the specific requirements of the biosensor component as follows: 16 to 22 weight % chromium and 7 to 12 weight % nickel; or 17 to 21 weight % chromium and 7 to 12 weight % nickel; or 18 to 20 weight % chromium and 7 to 12 weight % nickel; or 16 to 22 weight % chromium and 8 to 11 weight % nickel; or 17 to 21 weight % chromium and 8 to 11 weight % nickel, or 18 to 20 weight % chromium and 8 to 11 weight % nickel. In certain embodiments, these metal alloys can also comprise at least 65 weight % iron; or 65 to 75 weight % iron, or 65 to 74 weight % iron; or 66 to 75 weight % iron, or 66 to 74 weight % iron.

The non-noble metal alloys that comprise the conductive layer of electrode, for example, the biosensor component, can also include iron. In various embodiments, the non-noble metal alloys can comprise at least about 2, 3, 4, 5, 6, or 7 and/or up to about 80, 75, or 74 weight percent of iron. In certain embodiments, the non-noble metal alloys can comprise in the range of 2 to less than 80, or about 2 to 75, 3 to 75, 4 to 75, 5 to 75, 6 to 75, 7 to 75, 2 to 74, 3 to 74, 4 to 74, 5 to 77, 6 to 74, 7 to 74 weight percent of iron, based on the total weight of the conductive layer equaling 100 weight percent. In certain embodiments, the non-noble metal alloys can comprise at least about 5, 6, or 7 and/or up to about 12, 11, 10, or 9 weight percent of iron. In certain embodiments, the non-noble metal alloys can comprise in the range of greater than 5 to less than 12, or about 6 to 11, 6 to 10, 6 to 9, 7 to 11, 7 to 10, 7 to 9, or about 9 weight percent of iron, based on the total weight of the conductive layer equaling 100 weight percent. In certain embodiments, the non-noble metal alloys can comprise at least about 60, 61, 62, 63, 64, 65 or 66 and/or up to about 80, 78, 76, 75 or 74 weight percent of iron. In certain embodiments, the non-noble metal alloys can comprise in the range of 60 to 80, or about 61 to 79, 62 to 78, 63 to 77, 64 to 76, 65 to 75, 65 to less than 75, 65 to 74, 66 to less than 75, or 66 to 74 weight percent of iron, based on the total weight of the conductive layer equaling 100 weight percent.

In certain embodiments, non-noble metal alloys other than nickel, chromium and iron that can be present in the invention can include one or more of Group I as follows: manganese and copper and/or one or more of Group II as follows: carbon and silicon. Weight percentages of all metal alloys useful in this invention are based on the total weight percentages of materials in the conductive layer equaling 100 weight percent.

In certain embodiments, the conductive layer can further comprise at least about 0.001, 0.01, or 0.1, and/or up to 2.0, 1.5, 1.0, 0.9, 0.8, 0.7 or 0.6 weight percent of manganese. In certain embodiments, the non-noble metal alloys can comprise in the range of about 0.001 to 2.0, less than about 2.0, 0.001 to 1.0, 0.01 to 1.0, 0.1 to 1.0, or less than about 1.0 weight percent of manganese.

In certain embodiments, the conductive layer can further comprise at least about 0.001, 0.01, 0.1, or 0.2 and/or up to about 1.0, 0.5, 0.4, or 0.3 weight percent of copper. In certain embodiments, the non-noble metal alloys can comprise in the range of about 0.001 to 1.0, less than about 1.0, 0.001 to 0.5, 0.01 to 0.5, 0.1 to 0.5, or less than about 0.5 weight percent of copper.

In certain embodiments, the conductive layer can further comprise a maximum of 3.0, 2.5, 2.0, 1.5, 1.0, 0.5, 0.3, 0.2, 0.1, 0.05 or 0.015 weight percent of silicon. In certain embodiments, the conductive layer can comprise a maximum of 0.15 weight percent of carbon.

In certain embodiments, the conductive layer contains molybdenum, if present, in an amount of 0 to 20, 0 to 15, 0 to 13, 0 to 10, 0 to 5, 0 to 4, 0 to 3, 0 to 2, or 0 to 1 weight percent, based on the total weight of the conductive layer. In certain embodiments, the conductive layer contains molybdenum, if present, in an amount less than 1, or less than 0.8, or less than 0.6, or less than 0.4, or less than 0.2, or less than 0.1 weight percent, based on the total weight of the conductive layer. In embodiments, the conductive layer is substantially free of molybdenum. In embodiments, the conductive layer contains no molybdenum.

In certain embodiments, the conductive layer contains less than 0.2 weight percent of each of the following element species: carbon, sulfur, phosphorous, molybdenum, niobium, cobalt, aluminum, titanium, or boron. In an embodiment, the conductive layer contains none, or is substantially free, of the following element species: molybdenum, niobium, cobalt, aluminum, titanium, or boron. In an embodiment, the conductive layer contains none of the following element species: molybdenum, niobium, cobalt, aluminum, titanium, or boron. In an embodiment, the conductive layer contains none or is substantially free of the following element species: molybdenum, niobium, cobalt, aluminum, titanium, phosphorus, or boron, or, in embodiments where any species is present, such species is in an amount of less than 0.25 weight percent, or less than 0.2 weight percent, or less than 0.1 weight percent, or less than 0.05 weight percent, or trace amounts or less. In certain embodiments, the conductive layer contains none or is substantially free of the following element species: molybdenum, niobium, cobalt, aluminum, titanium, phosphorus, or boron. In an embodiment, the conductive layer contains none or is substantially free of the following element species: molybdenum, copper, niobium, cobalt, aluminum, titanium, or boron, or, in embodiments where any species is present, such species is in an amount of less than 0.25 weight percent, or less than 0.2 weight percent, or less than 0.1 weight percent, or less than 0.05 weight percent, or trace amounts or less. In certain embodiments, the conductive layer contains none or is substantially free of the following element species: molybdenum, copper, niobium, cobalt, aluminum, titanium, or boron.

In certain embodiments, the amount of nickel, chromium and iron included in the non-noble metal alloys that comprise the conductive layer of electrode, for example, the biosensor component, can vary depending on the specific requirements of the biosensor component as follows: 10 to 30 weight % chromium, 8 to 75 weight % nickel and 2 to 75 weight % iron; or 10 to 25 weight % chromium, 8 to 75 weight % nickel and 3 to 75 weight % iron; or 10 to 25 weight % chromium, 8 to 75 weight % nickel and 4 to 75 weight % iron; or 10 to 25 weight % chromium, 8 to 75 weight % nickel and 5 to 75 weight % iron; or 13 to 21 weight % chromium, 8 to 73 weight % nickel and 6 to 75 weight % iron, or 14 to 20 weight % chromium, 8 to 72 weight % nickel and 6 to 74 weight % iron, all of these weight percentages being based on the total weight percentages of the conductive layer equaling 100 weight percent.

In certain embodiments, the amount of nickel, chromium and iron included in the non-noble metal alloys that comprise the conductive layer of electrode, for example, the biosensor component, can vary depending on the specific requirements of the biosensor component as follows: 13 to 25 weight % chromium, 70 to 81 weight % nickel and greater than 5 to less than 12 weight % iron; or 13 to 20 weight % chromium, 70 to 81 weight % nickel and 6 to 11 weight % iron; or 13 to 18 weight % chromium, 70 to 81 weight % nickel and 6 to 11 weight % iron; or 14 to 17 weight % chromium, 70 to 81 weight % nickel and 6 to 11 weight % iron; or 13 to 18 weight % chromium, 72 to 81 weight % nickel and 6 to 11 weight % iron, or 14 to 17 weight % chromium, 72 to 81 weight % nickel and 6 to 11 weight % iron; or 14 to 17 weight % chromium, 72 to 81 weight % nickel and 6 to 10 weight % iron, all of these weight percentages being based on the total weight percentages of the conductive layer equaling 100 weight percent.

In certain embodiments, the amount of nickel, chromium and iron included in the non-noble metal alloys that comprise the conductive layer of electrode, for example, the biosensor component, can vary depending on the specific requirements of the biosensor component as follows: 16 to 22 weight % chromium, 7 to 12 weight % nickel and 65 to 75 weight % iron; or 17 to 21 weight % chromium, 7 to 12 weight % nickel and 65 to 75 weight % iron; or 18 to 20 weight % chromium, 7 to 12 weight % nickel and 65 to 75 weight % iron; or 16 to 22 weight % chromium, 8 to 12 weight % nickel and 65 to 75 weight % iron; or 16 to 22 weight % chromium, 8 to 11 weight % nickel and 65 to 75 weight % iron, or 18 to 20 weight % chromium, 8 to 11 weight % nickel and 66 to 74 weight % iron, all of these weight percentages being based on the total weight percentages of the conductive layer equaling 100 weight percent.

Conductive layers in the present disclosure can be constructed of a single layer comprising any of the alloy compositions disclosed in this application. In certain embodiments, the alloy composition contains an alloy which can be a solid solution of the elements (a single phase), a mixture of metallic phases (two or more solutions) or an intermetallic compound with no distinct boundary between the phases.

As one skilled in the art would readily appreciate, the elements of the non-noble metal alloys may comprise incidental impurities. As used herein, “incidental impurities” refer to any impurities that naturally occur in the ore used to the produce the non-noble metal alloys or that are inadvertently added during the production process. The non-noble metal alloys can comprise less than about 0.1, 0.05, or 0.001 weight percent of the incidental impurities.

The non-noble metal alloys described herein may also contain one or more additional alloying elements, which are in addition to the elements described above. However, in various embodiments, the non-noble metal alloys can be substantially free from such additional alloying elements. As used herein, the terms “practically free” and “substantially free” mean that the non-noble metal alloy comprises less than 0.001 weight percent of such additional alloying components. Furthermore, the terms “practically free” and “substantially free” may be used interchangeably.

In certain embodiments of the present disclosure, the biosensor components described herein can be prepared by performing the following steps:

(a) providing a substrate;

(b) providing a conductive layer target;

(c) physical vapor depositing at least a portion of the substrate with material from the target to thereby form a conductive layer on the substrate;

(d) providing a resistive material target;

(e) physical vapor depositing at least a portion of the conductive layer with material from the resistive material target to thereby form a resistive material layer on the substrate.

The providing a substrate of step (a) may include the provision of any type of substrate material, such as PET, as was previously described. In certain embodiments, the substrate will comprise a sheet of substrate material that can be actuated within a high vacuum chamber. The sheet of substrate material may comprise a single section of material, such as a square sheet. In some other embodiments, sheet of substrate material may comprise a roll of material that is passed, via a roll-to-roll mechanism, through the high vacuum chamber, as will be described in more detail below. In other embodiments, the substrate may be held stationary or may be rotated during deposition, as will be also described below.

The providing a target of step (b) may include the provision of a physical vapor deposition target comprised of any of the non-noble metal alloys previously described. For example, in some embodiments, the physical vapor deposition targets comprising the alloys listed in Table 1 were used to make thin film conductive layers. Such alloy targets may comprise less than about 0.1, 0.05, or 0.001 weight percent of incidental impurities. In some embodiments, the physical vapor deposition target will be housed within and/or will comprise an electrode, such as a sputter cathode, during the physical vapor deposition process. In certain embodiments, the physical vapor deposition target may be a circular, having a diameter of at least 2, 4, 8, 12, 16, or 20 cm. In other embodiments, the physical vapor deposition target may be a tubular target having an inner diameter of at least 2, 4, 8, or 16 cm and an outer diameter of 20, 24, 28 or 32 cm. In still other embodiments, the physical vapor deposition target may be rectangular with dimensions of: a width of between 5 to 25 cm, a length of between 25 to 75 cm, and a thickness of between 0.3 to 5 cm. It should be understood, however, that embodiments of the present disclosure contemplate the use of other-shaped and sized targets.

The physical vapor depositing of step (c) generally includes the coating of the substrate with the material from the non-noble metal alloy target to form the conductive layer. As used herein, the term “physical vapor deposition” shall denote depositing thin-films by providing for the condensation of vaporized material onto a substrate. The physical vapor deposited coating may be performed with any type of physical vapor deposition process previously described, i.e., sputter coating, thermal evaporation, electron beam evaporation, laser ablation, arc vaporization, co-evaporation, ion plating, or the like. For example, in some embodiments, the physical vapor depositing step will be performed via a sputtering process, in which the substrate is coated with the conductive layer by sputtering the non-noble metal alloy target via the sputtering device. Specific examples of such a sputtering-type physical vapor depositing will be described in more detail below. The resulting substrate with the conductive layer coated thereon may be used as a biosensor component, such as an electrode. Such electrodes may include a working electrode, a reference electrode, and/or a counter electrode. In certain embodiments, such as when a roll of substrate material is vacuum coated with a conductive layer, via a roll-to-roll physical vapor deposition process, the resulting thin-film sheet may be cut apart to appropriate size to form a thin-film electrode specifically sized for the biosensor component. In other embodiments, the biosensor components can be formed from the thin-film sheet by etching, such as chemical or laser etching. In still other embodiments, the biosensor components can be formed using a patterned mask, which is laid on the substrate, and the conductive layer is physical vapor deposited thereover to form the conductive layer of a biosensor component.

The providing a target of step (d) may include the provision of a physical vapor deposition target comprised of any of the resistive materials previously described. For example, in some embodiments, the physical vapor deposition targets comprising carbon were used to make thin film amorphous carbon layers. Such resistive material targets may comprise less than about 0.1, 0.05, or 0.001 weight percent of incidental impurities. In embodiments, a target can include materials that can differ from the deposited resistive layer material but, when used as the source material for physical vapor deposition, produce the resistive material. It should be understood that the resistive material target can have a different composition and/or structure than the deposited resistive material. In some embodiments, the physical vapor deposition target will be housed within and/or will comprise an electrode, such as a sputter cathode, during the physical vapor deposition process. In certain embodiments, the physical vapor deposition target may be a circular, having a diameter of at least 2, 4, 8, 12, 16, or 20 cm. In other embodiments, the physical vapor deposition target may be a tubular target having an inner diameter of at least 2, 4, 8, or 16 cm and an outer diameter of 20, 24, 28 or 32 cm. In still other embodiments, the physical vapor deposition target may be rectangular with dimensions of: a width of from 5 to 25 cm, a length of between 25 to 75 cm, and a thickness of from 0.3 to 5 cm. It should be understood, however, that embodiments of the present disclosure contemplate the use of other-shaped and sized targets.

The physical vapor depositing of step (e) generally includes the coating of the substrate with the material from the resistive material target to form the resistive material layer. As used herein, the term “physical vapor deposition” shall denote depositing thin-films by providing for the condensation of vaporized material onto a substrate. The physical vapor deposited coating may be performed with any type of physical vapor deposition process previously described, e.g., sputter coating, thermal evaporation, electron beam evaporation, arc vaporization, co-evaporation, ion plating, or the like. For example, in some embodiments, the physical vapor depositing step will be performed via a sputtering process, in which the conductive layer (previously deposited on the substrate) is coated with the resistive material layer by sputtering the resistive material target via the sputtering device. Specific examples of such a sputtering-type physical vapor depositing will be described in more detail below. The resulting substrate with the conductive layer and resistive material layer coated thereon may be used as a biosensor component, such as an electrode. In embodiments, the “resistive material” layer is a generally distinct layer from the conductive layer, forming a laminar structure, where there is a distinct interface between the layers so that each of the resistive material layer and conductive layer are separate and distinct layers, having different compositions.

In certain embodiments, such as when a roll of substrate material is vacuum coated with a conductive layer, via a roll-to-roll physical vapor deposition process, the resulting thin-film sheet may be cut apart to appropriate size to form a thin-film electrode specifically sized for the biosensor component. Such electrodes may include a working electrode, a reference electrode, and/or a counter electrode. Electrodes may also include those for the detection of conductivity of a sample, whether or not a sample has been applied to the biosensor component, or other electrical characteristics of the sample or sample environment that is useful for a biosensor. In other embodiments, the biosensor components can be formed from the thin-film sheet by etching, such as chemical or laser etching. In still other embodiments, the biosensor components can be formed using a patterned mask, which is laid on the substrate and conductive layer, and the resistive material layer is physical vapor deposited thereover to form the biosensor component.

In certain specific embodiments, the biosensor components may be created via a roll-to-roll physical vapor deposition process that includes roll-to-roll magnetron sputtering. For instance, a substrate sheet comprising a polymer film made of PET (polyethylene terepthalate) with a thickness ranging from 25 μm to 250 μm and width of 33.02 cm may be sputtered using a 77.50 cm wide web roll-to-roll magnetron sputter coater, such as a the Smartweb coater offered by Applied Materials, Inc. or the Mark 80 offered by CHA Industries, Inc. A single or a dual target configuration can be employed to deposit a conductive layer of non-noble metal alloys, such as certain alloys from Table 1. A target comprised of a non-noble metal alloy plate (such as is available from Tricor Industries Inc.) can be used. A vacuum chamber of the sputter coater can be pumped down to base pressure of at least 10⁻⁵ Torr using a diffusion and mechanical pump combination. In other embodiments a combination of a mechanical pump, a turbo pump, a cryo pump, and/or an oil diffusion pump may be used. Magnetron sputtering cathodes housing the non-noble metal alloy targets having a generally rectangular shape can be energized using 2 KW power supplies (such as offered from Advanced Energy Inc.). An argon gas flow into the vacuum chamber can be controlled (such as via a MKS model 1179A flow controller) to set a sputtering pressure between 3 to 10 mTorr for use during the sputtering process.

Thickness and sheet resistance of the sputtered conductive layer can be efficiently controlled in-situ by controlling specific process parameters. Examples of process parameters include roll-to-roll web speeds (, i.e., controlling the speed of the substrate sheet as it travels through the vacuum chamber during sputtering), power supplied to the sputtering targets (i.e. a product of the applied voltage and current to the plasma formed near the target surface), gas pressure in the sputtering chamber, and the number of targets present in the chamber. For example, for sputtering of a conductive layer of a given alloy, the web speed can be set to between 0.1 to 3.5 meters per minute and sputtering power density of from 1 to 8 Watts per square cm. In embodiments, sputtered conductive layer of the alloy may be formed having a measured thickness value of about 25 nm and a sheet resistance of about 45 ohms per square.

The resistive material layer can be deposited on top of the conductive layer via one of the deposition techniques described above. For example, in one embodiment the resistive layer can be deposited using DC magnetron sputtering from a carbon target. The thickness of the resistive material layer can be controlled by controlling specific process parameters. Examples of process parameters include roll-to-roll web speeds (i.e., controlling the speed of the substrate sheet as it travels through the vacuum chamber during sputtering), power supplied to the sputtering targets (i.e., a function of the applied voltage and current to the plasma formed near the target surface), gas pressure in the sputtering chamber, and the number of targets present in the chamber. For example, in certain embodiments, for sputtering of a resistive layer on a given alloy, the web speed can be set to from 0.1 to 3.5 meters per minute and sputtering power density of from 1 to 8 Watts per square cm. In embodiments, the sputtered resistive layer may be formed having a measured thickness value of about 1-200 nm.

In addition to the roll-to-roll process described above, biosensor components can be manufacture using a scaled-up version of the same geometry, using a large-scale roll-to-roll process. In such a large-scale roll-to-roll process, maximum web speeds can be 0.1 to 10 meters per minute, between 3 to 7 meters per minute, or higher than 10 meters per minute. The large-scale roll-to-roll process may provide a sputtering power density between 0.1 to 13, 2 to 10, or 5 to 8 Watts per square cm. Additionally, the number of targets can include between 2, 4, 6 or more, and the web width of the substrate sheet can be from 75 cm or larger.

Embodiments additionally contemplate that physical vapor deposition processes can be utilized in which substrate sheets are held stationary within the vacuum chamber. Certain of such embodiments, are described in detail below in the Examples section. In some embodiments in which the substrate sheets are held stationary, deposition times for depositing the conductive layer on the substrate sheets may be 5, 10, 15, 30 minutes or more.

As previously noted above, biosensor components that include a conductive layer formed from the non-noble metal alloys and a resistive material layer, as described herein, can exhibit desirable electrochemical properties that make them particularly well suited as replacements for biosensor components that incorporate noble metals, such as palladium and/or gold. For instance, the biosensor components of embodiments of the present disclosure may comprise a thin-film electrode formed with a non-noble metal alloy conductive layer and a resistive material layer that exhibits desirable dose-response characteristics when undergoing chronoamperometry tests.

In various embodiments, the conductive layer can comprise nickel, chromium, and iron (in amounts as discussed above) and the conductive layer and resistive material layer combination can have an oxidation wave voltage for Fe(II)[CN]₆ mediator (identified below as E_(peak,anodic)) of less than 400, or less than 390, or less than 380, or less than 375, or less than 360, or less than 350, or less than 340, or less than 330, or less than 325, or less than 320, or less than 310, or less than 300, or less than 290, or less than 280, or less than 275, or less than 270, or less than 260 millivolts (mV), as determined in a Type 1 Linear Sweep Voltammetry Test (as discussed in the Examples section).

This invention can be further illustrated by the following examples of embodiments thereof, although it will be understood that these examples are included merely for the purposes of illustration and are not intended to limit the scope of the invention unless otherwise specifically indicated.

EXAMPLES

Preparation of Thin-Film Electrodes

For each of the below-described examples (and comparative examples), biosensor components in the form of thin-film electrodes were formed by the following-described physical vapor deposition process. It is understood that thin-film electrodes can be formed, using the below process, to include a conductive layer of a plurality of different types of elements and element alloys, such as the non-noble compositions listed in Table 1. In most examples, these thin film electrodes also included a carbon resistive material layer that was deposited on top of the conductive layer, except where indicated otherwise. The process included forming thin-film electrode films by:

-   -   (a) metal or metal alloys were deposited on 10.16 cm×10.16 cm         square PET substrate sheet using direct current (“DC”) magnetron         sputtering in a high vacuum chamber, with the sputtering having         been performed with a Denton Vacuum Desktop Pro sputtering         device;     -   (b) the vacuum chamber was evacuated to an initial base pressure         of ˜10⁻⁵ Torr;     -   (c) argon gas of 10 sccm was introduced into the high vacuum         chamber to create a deposition pressure of 4 mTorr;     -   (d) the substrate sheets were rotated at approximately two         revolutions per minute within the vacuum chamber;     -   (e) a 5.08 cm diameter target of the metal or metal alloys was         held at a constant power of 40 Watts under the DC magnetron         sputtering device for deposition time of 15 minutes to coat at         least a portion of the substrate sheet with the conductive layer         (to initialize the targets, the targets were held at a constant         power of 40 Watts under the DC magnetron sputtering device for a         5 minute pre-sputtering time prior to the substrates being         introduced into the vacuum chamber);     -   (f) following the deposition of the conductive layer, carbon         layer was then be deposited. A 5.08 cm diameter target of         graphite material was held at a constant power of 40 Watts under         the DC magnetron sputtering device for deposition time of 15         minutes to coat at least a portion of the conductive layer         (deposited in step e) with a carbon layer (to initialize the         targets, the targets were held at a constant power of 40 Watts         under the DC magnetron sputtering device for a 5 minute         pre-sputtering time prior to the conductive layer coated         substrate being introduced into the vacuum chamber); and     -   (g) all depositions were carried out at room temperature.

Individual thin-film electrodes, with a size of 5.08 cm×7.62 cm, were cut from the thin-film electrode films that were formed by physical vapor deposition, as provided above. Electrochemical experiments were conducted using a Gamry Instruments Reference 600 potentiostat in a three electrode configuration, with the electrochemical cell containing the thin-film electrode film positioned inside of a Gamry Instruments VistaShield Faraday Cage. Each of the thin-film electrodes was formed as a working electrode by partially masking the thin-film electrode with electroplating tape having a single 3 mm diameter aperture die-cut into it. As such, an unmasked portion formed by the die-cut aperture of the thin-film electrode provided a geometric working electrode surface area of 0.0707 square cm. Another different area of unmasked portion of the thin-film electrode served as an electrical connection point to a working electrode lead of the potentiostat. The masked portion of the thin-film electrode was placed onto a flat supporting block of non-conductive material, such as plastic. The thin-film electrode was thereafter placed into a working electrode port of a glass electrochemical cell. The exposed 3 mm diameter portion of the thin-film electrode was positioned near a center of a bottom opening of working electrode port of the electrochemical cell. The working electrode port of the electrochemical cell was sealed with a clamp and an O-ring. The electrochemical cell also contained a reference electrode comprising a saturated calomel reference electrode and a carbon auxiliary electrode. The reference electrode and the auxiliary electrode were placed, respectively in a reference electrode port and an auxiliary electrode port. Additionally, the reference electrode and the auxiliary electrode were connected, respectively, to a reference lead and an auxiliary lead of the potentiostat. The electrochemical cell also included a gas flow port by which to deaerate and blanket test solutions with inert gas, such as nitrogen.

Thin film electrodes were prepared from a stainless steel 316 alloy, both with and without a carbon resistive material layer, according to the procedures discussed above.

Additional thin film electrodes were prepared from alloys containing varying amounts of nickel, chromium and/or iron according to the procedures discussed above. The alloys used were Inconel® 600 (In600), Stainless Steel 304 (SS304), Hastelloy® C-22 (C22), Hastelloy® B3 (B3), and pure Ni. The specific alloy compositions are listed below in Table 1. The thin film electrodes having conductive layers as listed in Table 1 also included a carbon resistive layer prepared according to the procedures discussed above. Carbon resistive layer thickness was approximately 15 nm as determined by TEM imaging of cross-sectioned electrodes.

TABLE 1 Alloys (source: www.specialmetals.com/alloys) Element (% by mass) Alloy Ni Cr Fe Mo W Co Mn Cu Al Ti Si C S P In600 72 (min) 14-17 6-10 2* 0.5* 0.5* 0.15* 0.015* SS304 8-10.5 18-20 66.35-74    1* 1*   0.08* 0.03*  0.045* C22 56 22 3 13 3    2.5*   0.5* 0.5*  0.08* 0.01* B3¹ 65 (min) 1.5 1.5 28.5 3* 3* 3* 0.2* 0.5* 0.2* 0.1* 0.01* Ni 100  *denotes maximum concentration ¹B3 alloy also includes elements V (0.2 max) and Cb (0.2 max) Type 1 Linear Sweep Voltammetry Test Description

A Type 1 Linear Sweep Voltammetry Test can be used to test the electrochemical response of the thin-film electrodes. The Type 1 Linear Sweep Voltammetry Test comprises the following steps: 50 mL of 10 mM potassium phosphate buffer containing 145 mM sodium chloride at pH 7.1 was placed into the electrochemical cell and the electrochemical cell was sealed with stoppers. Gas inlet and outlet fittings, which were associated with the gas flow port, allowed inert gas sparging (i.e., de-aerating) of the buffer solution, via a gas flow of nitrogen, using a medium-porous filter stick. The gas flow port additionally allowed the gas flow to be switched from the filter stick to a headspace-blanketing arrangement. The gas outlet was connected to an oil bubbler to prevent back-diffusion of external gas (e.g., air) into the electrochemical cell. The buffer solution was stirred with a magnetic stirbar while simultaneously sparged with nitrogen for at least 5 minutes before switching the gas flow to a blanketing configuration. No agitation of the buffer solution from sparging or otherwise was otherwise present during the electrochemical experiments conducted via the Type 1 Linear Sweep Voltammetry Test (i.e., the solution was quiescent during electrochemical testing).

A linear sweep voltammetry test was performed on the thin-film electrode that comprised the working electrode within the electrochemical cell. The initial voltage potential for linear sweep voltammetry was 0 V versus the open circuit potential (also known as the rest potential), as measured between the working electrode and the reference electrode (i.e., the saturated calomel reference electrode), and after a rest period of at least 10 seconds prior to the voltammetric experiment, the voltage potential was swept anodically at 25 mV per second until a current of at least 50 μA was observed. For solutions that contained Fe(II)[CN]6 mediator, the mediator was present at 1 or 2 mM concentration and the linear sweep voltammetry conditions were otherwise identical to mediator-free solutions.

A peak voltage (“E_(peak,anodic)”) of the oxidation wave is determined, with such E_(peak,anodic) being defined as the voltage at which a local maximum of current is observed as a result of the oxidation of an electroactive species in solution, as measured between the working electrode and the counter electrode versus the reference electrode. An illustration of an oxidation wave and an associated E_(peak,anodic), as obtained from a thin-film electrode using the Type 1 Linear Sweep Voltammetry Test, is illustrated in FIG. 3 . As can be seen from FIG. 3 , the measured E_(peak,anodic) (or E-peak) value was approximately −76 mV, as measured versus a reference electrode.

Application of Type 1 Linear Sweep Voltammetry Test to Thin-Film Electrodes

A plurality of different thin-film electrodes were tested using the Type 1 Linear Sweep Voltammetry Test. In more detail, thin-film electrodes formed with a stainless steel 316 (SS316) conductive layer, both without a resistive material layer deposited thereon and with an amorphous carbon layer deposited thereon (C on SS316) were tested. Additionally, thin-film electrodes formed with a conductive layer selected from each of the non-noble metal alloys listed in Table 1 and capped with an amorphous carbon layer were tested.

The results of such tests are illustrated graphically in FIGS. 3-4 . It can be generally desirable for the thin-film electrodes used in biosensors to exhibit a peak anodic current for Fe(II)[CN]₆ that occurs at a voltage as low as possible. It can also generally be desirable for the thin-film electrodes used in biosensors to exhibit minimized and/or reduced currents under the influence of certain electrode potentials. FIG. 3 is a plot of a Type 1 linear sweep voltammetry test conducted on thin-film electrode of SS316 and C on SS316. As illustrated in FIG. 3 , the thin-film electrode showed both improved heterogeneous electron transfer kinetics with Fe(II)[CN]₆ and anodic stability for the C on SS316 electrode, compared to the SS316 electrodes without a carbon layer.

FIG. 4 is a plot of a Type 1 linear sweep voltammetry test conducted on the alloys from Table 1 using a phosphate buffer solution and a Fe(II)[CN]₆ mediator, and illustrates the heterogeneous electron transfer kinetics with the Fe(II)[CN]₆ mediator for these alloys as indicated by the voltage at which oxidation of Fe(II)[CN]₆ occurs. Generally, it may be desirable for an electrode material in a sensor such as a blood glucose sensor to have as fast as possible heterogenous electron transfer kinetics so that the applied oxidizing voltage that is required to operate the sensor is as small as possible. In some embodiments, a biosensor may be operated at a voltage sufficiently anodic to cause the working electrode current to be controlled by the diffusion of electroactive species (e.g., mediator). If the applied voltage is too oxidizing, oxidation of interferent species that might be present in blood, such as uric acid, acetaminophen, and the like, might be oxidized. This could result in undesired positive bias in the determined glucose concentration and a less accurate sensor. A review of FIG. 4 reveals that heterogeneous electron transfer kinetics with ferrocyanide was generally acceptable for the electrodes made with Inconel® 600 (In600), Stainless Steel 304 (SS304), and Hastelloy® C-22 (C22), with the C-22 and SS304 having slightly faster heterogeneous electron transfer than In600. The electrodes made using Hastelloy® B3 (B3) and pure Ni were unacceptable. This was due to these electrodes having anodic breakdown potentials that are too close to the redox couple of the redox mediator Fe(II)[CN]₆. Having an anodic breakdown potential close to the redox couple of the mediator can cause an increase in background noise during the electrochemical measurement.

Mechanical Flexibility Analysis Using Mandrel Bend Testing of Thin-Film Electrodes

Mechanical flexibility of different films were analyzed using mandrel bend testing. The films that were tested were made according to the above procedures and include conductive layers of Cr, SS304, In600 and Mo, each having a carbon resistive layer.

Mandrel bend testing was carried out using the following apparatus:

-   -   a. Multimeter—A multimeter/ohmmeter capable of measuring         resistance to an accuracy of 0.01 ohms.     -   b. Probe—A resistance probe for measuring thin films that makes         contact with the film orthogonal to the long dimension of the         film in two locations contacting the full width of the film with         the contacts spaced two inches apart along the long axis.     -   c. Mandrels—Mandrels with diameters of ⅛″, ¼″, ½″, ⅝″ and having         surfaces than are smooth and clean and that are mounted on ball         bearings at each end so that the mandrel can rotate smoothly and         easily.

Mandrel testing was carried out by first examining the coating by eye and ensuring that the coating surface was free of scratches, creases, wrinkles, and torn edges. The thin film electrode to be tested was cut into a 2 inch wide strip and a length of at least 9 inches. Care was taken to avoid any cracks while cutting the film.

The cut film was then tested as follows:

-   -   a. The initial sheet resistance (Ro) in ohms/sq was measured and         recorded using a 2 inch resistance probe along the length of         test sample, with measurements taken at 3 inch intervals.     -   b. The film was then bent around the ⅝″ mandrel so that the         coated side was in contact with the mandrel.     -   c. The ends of the film were held simultaneously and enough         tension was applied to the film to ensure firm contact with the         mandrel.     -   d. The film was pulled back and forth while carefully applying         gentle pressure on the film against the mandrel to let the         mandrel roll against the coating. Care was taken to make sure         that the film was rolling against the mandrel, not sliding, to         avoid scratches. The area of coating that was tested was marked.     -   e. Step d. was performed for 3 cycles or 6 strokes.     -   f. Sheet resistance (R) in ohms/sq was measured and recorded         using the 2 inch resistance probe along the length of test         sample length were the mandrel was contacted during the test,         with measurements taken at 3 inch interval over the test area.

The mandrel testing was repeated for all films using the above procedure, except the back (non-coated) side of the substrate was in contact with the mandrel surface.

The results of the mandrel testing with a comparison of the final sheet resistance (R) to initial sheet resistance (Ro) are shown in FIGS. 5 and 6 . A review of these figures reveals that the C on Mo and C on In600 are best, followed by C on SS304, with C on Cr having the lowest mechanical stability. FIGS. 5 and 6 reveal that the electrodes made using C on SS304 and C on In600 both were more mechanically robust than an electrode made using C on Cr, with the C on In600 having better mechanical robustness than C on SS304. Thin film electrodes that have better relative mechanical integrity as demonstrated by this test are believed to be more desirable for improved manufacturing robustness of web and sheet-based processes. When comparing two films using the mandrel tests described above, it is believed that the better performing film is indicative of more robust mechanical performance and improved repeatability and consistency for processing and using the thin-film electrode film in biosensor applications.

The above detailed description of embodiments of the disclosure is intended to describe various aspects of the invention in sufficient detail to enable those skilled in the art to practice the invention. Other embodiments can be utilized and changes can be made without departing from the scope of the invention. The above detailed description is, therefore, not to be taken in a limiting sense. The scope of the present invention is defined only by claims presented in subsequent regular utility applications, along with the full scope of equivalents to which such claims are entitled.

In this description, references to “one embodiment,” “an embodiment,” or “embodiments” mean that the feature or features being referred to are included in at least one embodiment of the technology. Separate references to “one embodiment”, “an embodiment”, or “embodiments” in this description do not necessarily refer to the same embodiment and are also not mutually exclusive unless so stated and/or except as will be readily apparent to those skilled in the art from the description. For example, a feature, step, etc. described in one embodiment may also be included in other embodiments, but is not necessarily included. Thus, the present technology can include a variety of combinations and/or integrations of the embodiments described herein.

The inventors hereby state their intent to rely on the Doctrine of Equivalents to determine and assess the reasonably fair scope of the present disclosure as it pertains to any apparatus not materially departing from but outside the literal scope of the invention as set forth in the following claims.

DEFINITIONS

It should be understood that the following is not intended to be an exclusive list of defined terms. Other definitions may be provided in the foregoing description, such as, for example, when accompanying the use of a defined term in context.

As used herein, the terms “a,” “an,” and “the” mean one or more.

As used herein, the term “and/or,” when used in a list of two or more items, means that any one of the listed items can be employed by itself or any combination of two or more of the listed items can be employed. For example, if a composition is described as containing components A, B, and/or C, the composition can contain A alone; B alone; C alone; A and B in combination; A and C in combination, B and C in combination; or A, B, and C in combination.

As used herein, the terms “comprising,” “comprises,” and “comprise” are open-ended transition terms used to transition from a subject recited before the term to one or more elements recited after the term, where the element or elements listed after the transition term are not necessarily the only elements that make up the subject.

As used herein, the terms “having,” “has,” and “have” have the same open-ended meaning as “comprising,” “comprises,” and “comprise” provided above.

As used herein, the terms “including,” “include,” and “included” have the same open-ended meaning as “comprising,” “comprises,” and “comprise” provided above.’

NUMERICAL RANGES

The present description uses numerical ranges to quantify certain parameters relating to the invention. It should be understood that when numerical ranges are provided, such ranges are to be construed as providing literal support for claim limitations that only recite the lower value of the range as well as claim limitations that only recite the upper value of the range. For example, a disclosed numerical range of 10 to 100 provides literal support for a claim reciting “greater than 10” (with no upper bounds) and a claim reciting “less than 100” (with no lower bounds). 

What is claimed is:
 1. A biosensor component for use in analyzing a biological sample, said biosensor component comprising: a substrate; a conductive layer deposited on said substrate; and a resistive material layer deposited on said conductive layer wherein said conductive layer comprises nickel, chromium and iron, wherein a combined weight percent of the nickel and chromium in the conductive layer is in the range of 25 to less than 95 weight percent, wherein the weight percent of nickel in the conductive layer is at least 4 weight percent, wherein the weight percent of chromium in the conductive layer is at least 10 weight percent, wherein the weight percent of iron in the conductive layer is at least 2 weight percent, wherein the conductive layer comprises 0 to 20 weight percent molybdenum, and wherein the resistive material layer comprises amorphous carbon and has a thickness in the range of 5 to 100 nm.
 2. The biosensor component according to claim 1, wherein said biosensor component comprises an electrode, wherein said electrode is a working electrode or a reference electrode or a counter electrode.
 3. The biosensor component according claim 1, wherein the biosensor component is a blood glucose sensor.
 4. The biosensor component according to claim 1, wherein said biosensor component comprises a test-strip.
 5. The biosensor component according to claim 1, wherein the weight percent of nickel in the conductive layer is in the range from about 8 to about 81 weight percent.
 6. The biosensor component according to claim 5, wherein the weight percent of chromium in the conductive layer is in the range from about 14 to about 20 weight percent.
 7. The biosensor component according to claim 6, wherein the weight percent of iron in the conductive layer is in the range from about 6 to about 74 weight percent.
 8. The biosensor component according to claim 1, wherein the weight percent of nickel in the conductive layer is in the range from about 70 to about 81 weight percent.
 9. The biosensor component according to claim 8, wherein the weight percent of chromium in the conductive layer is in the range from about 14 to about 17 weight percent.
 10. The biosensor component according to claim 9, wherein the weight percent of iron in the conductive layer is in the range from about 6 to about 10 weight percent.
 11. The biosensor component according to claim 1, wherein the weight percent of nickel in the conductive layer is in the range from about 8 to about 11 weight percent.
 12. The biosensor component according to claim 11, wherein the weight percent of chromium in the conductive layer is in the range from about 18 to about 20 weight percent.
 13. The biosensor component according to claim 12, wherein the weight percent of iron in the conductive layer is in the range from about 65 to about 75 weight percent.
 14. The biosensor component according to claim 1, wherein the conductive layer comprises 0 to 13 weight percent molybdenum.
 15. The biosensor component according to claim 1, wherein the conductive layer comprises no molybdenum.
 16. The biosensor component according to claim 1, wherein said substrate comprise polyethylene terephthalate (PET), and wherein said resistive material layer comprises amorphous carbon and has a thickness in the range from 5 to less than 20 nm.
 17. A method for forming the biosensor component of claim 1, comprising: (a) providing the substrate; (b) providing a conductive material target; (c) physical vapor depositing at least a portion of said substrate with material from said conductive material target to thereby form the conductive layer on said substrate; (d) providing a resistive material target; and (e) physical vapor depositing at least a portion of said conductive layer with material from said resistive material target to thereby form the resistive material layer on said conductive layer.
 18. The method of claim 17, wherein said substrate comprise polyethylene terephthalate (PET), wherein said substrate has a thickness in the range from 25 and 500 μm, said conductive layer has a thickness of in the range from 15 and 200 nm, and said resistive material layer has a thickness in the range from 5 to 50 nm, wherein said electrode has a visible light transmission of no more than 20%, wherein the biosensor comprises a blood glucose sensor.
 19. The method of claim 17, wherein said substrate comprise polyethylene terephthalate (PET), wherein said resistive material layer comprises amorphous carbon and has a thickness in the range from 5 to less than 20 nm. 